Ch10-120305 - CHEM 350: Introduction to Biological...

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Unformatted text preview: CHEM 350: Introduction to Biological Chemistry Brian Lee, Ph.D. Office: Neckers 146G or 324 Phone: 453-7186 Ho urs: 9:30am to 10:30am or by appointment Website: https:/ / Textbook (required, U.S. edition only) Fundamentals of Biochemistry, 3rd Ed., Voet, Voet & Pratt. Study Guide (recommended) Student Companion to Fundamentals of Biochemistry, 3rd Ed. Help Desk Tuesday 6:30 to 7:30 pm in Neckers 218 Thursday 5:00 to 6:00 pm in Neckers 410 Announcements Undergraduate Research Opportunities Research for credit (such as CHEM 396 or CHEM 496) Student worker ($8.00 per hour) ( Undergraduate Assistantships ( McNair Scholars Program ( REACH Awards Competition ( Summer Research Experiences for Undergraduates (REU) Deadline for SIUC REU Program is March 7th For other REU programs, search the National Science Foundation site: Students must contact the individual sites for information and application materials. NSF does not have application materials and does not select student participants. A contact person and contact information is listed for each site. Assignments Read Chapter 11 Enzymatic Catalysis Chapter 11 Problems Student Companion site for Voet, Voet & Pratt Third Midterm Exam, Wednesday March 28th Chapters 10-13 Help Desk Tuesday 6:30 to 7:30 pm in Neckers 218 Thursday 5:00 to 6:00 pm in Neckers 410 1. 2. 3. 6. Membrane Transport 5. Ion Channels 4. Passive mediated transport (facilitated diffusion) Ion selective channels – often coupled to other transporters Extremely efficient - diffusion limited rate of transport. Selective filter mechanism distinguishes ions for transport. KcsA structure from Roderick MacKinnon K+ Channel-high selectivity for K+ homotetramer w ith 45 Å channel selectivity filter (3 Å) 10 Å cavity hydrated cyto plasmic anionic tunnel Selection filter has the signature sequence TVGYG which strips away water molecules and binds to K+ ions with carbonyl oxygens. Only K+ can coordinate all 4 carbonyl oxygens. Na+ would only bind 2. Lower affinity for Na+ gives 10,000 fold selectivity. K+ Channel (KcsA) high selectivity for K+ Due to electrostatic repulsion only positions 1,3 and 2,4 are occupied at a given time 1 2 3 4 Selectivity Filter only showing backbone carbonyls of two subunits Na+ Channel: Voltage-gated ion channel, sense a reduction in the transmembrane electrical potential and respond by opening. Highly selective for Na+ through charge interactions and size discrimination. Na+ Channel: Activation gate is linked to the voltage sensor that contains basic residues within the membrane that sense the membrane potential. (fishing float) Na+ Channel: Inactivation gate closes soon after the activation gate opens. The longer the tether the longer the open period. The Kv channel is a voltage sensing K+ channel that uses a similar mechanism to sense the change in membrane potential through helix S4. The bridging S4-S5 helix acts as a lever to open the channel Ligand-gated ion channel: Nicotinic Acetylcholine Receptor in addition to acetylcholine able to bind nicotine Nicotinic Acetylcholine Receptor: Binding of acetylcholine causes a conformational change, the channel opens and allows passage of Na+, Ca2+ and K+. The plasma membrane gets depolarized triggering a muscle contraction or propagation of the nerve impulse. non-polar channel polar channel Ligand-gated ion channel: Nicotinic acetylcholine receptor Allosteric protein, positively cooperative (binding to the 1st site increases affinity of the second site). nAChR is a heterohexamer. The subunit composition varies: - - - - in electric ray. ACh binding sites are between subunits: - and - Membrane Potential is maintained by ion pumps such as Na+K+ ATPase Changes in membrane potential can act as a signal or trigger for activation of other ion channels such as voltage gated Na+ channel Role of voltage-gated and ligand-gated ion channels in neural transmission 1) action potential - local depolarization of the membrane potential activates Na+ channel 2) voltage gated Ca2+ o pen to allow entry of Ca2+, a second messenger 3) Ca2+ triggers exocytotic release of acetylcholine 4) acetylcholine activates post-synaptic receptor 5) influx of ions creates an action potential in the post-synaptic nerve cell Na+ channel propagates the action potential by depolarizing membrane. K+ channel returns membrane potential to resting state. Figure 10-6b Figure 10-6a 1. 2. 6. Ionophore 3. Transport 5. 4. Figure 10-1 Ionophores: molecules that increase the permeability of membranes to ions (carrier ionophores and channel-forming ionophores) Valinomycin: Antibiotic, carries K+ across membranes down its concentration gradient Carrier ionophores bind ions and diffuse through the membrane to release them on the other side Valinomycin is a cyclical peptide with 3 repeats of 4 residues. The Valine carbonyl oxygens ligand to K+ with an octahedral geometry. Size discrimination between K+ and Na+ is 10,000 fold. Aquaporin, AQP-1 tetramer: movement of water molecules across membranes. Note: the water channel is in each subunit. NPA-water specificity. Pore allows passage of H2O but not H3O+ (change membrane electrochemical potentials). Arg and His repel H3O+. Cavity restricts H2O passage limiting proton hopping. Conserved Asn residues provide hydrogen bonds that reorient water molecule and break bonds to other water molecules. ...
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This note was uploaded on 03/26/2012 for the course CHEM 350 taught by Professor Lee during the Spring '08 term at SIU Carbondale.

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